Significant advances in the field of prostate cancer were highlighted during the 2023 AUA Annual Meeting. As the presenters of the Take Home Messages for Prostate Cancer, we had the opportunity to highlight some of the exciting new knowledge and discoveries presented, including updated AUA/SUO (Society of Urologic Oncology) guidelines and several exciting and important studies.

This presentation allowed for review of the updated AUA/SUO Guidelines for the Early Detection of Prostate Cancer.^1,2 The new guidelines emphasize personalized screening for patients based on clinical risk and shared decision-making, starting with PSA as the first screening test. The guidelines recommend to start screening for average-risk individuals between the ages of 45 and 50, while high-risk individuals (such as African American men and those with a positive family history) start between the ages of 40 and 45. Although regular screening was recommended every 2 to 4 years, it is important to emphasize that plans should be tailored to the individual through shared decision-making. For those at low risk for clinically significant disease, a biopsy could be forgone. Individuals with elevated risk or PSA should undergo further risk assessment, including use of established risk calculators. Prostate MRI or adjunctive biomarkers can provide further prebiopsy risk stratification with systematic biopsy and targeted biopsy of MRI lesions, if present, with 2 or more cores. Of note, if a biopsy showed 1 core with high-grade prostatic intraepithelial neoplasia there is no need for immediate repeat biopsy. For patients with a negative biopsy, it is not recommended to discontinue screening based on that biopsy or PSA threshold alone. Risk assessment tools that incorporate the effect of negative biopsy can also aid decisions regarding continued screening.

Beyond changes in guidelines, there have been other interesting discussions about the evaluation and treatment of prostate cancer. One example is the debate about transperineal vs transrectal prostate biopsy. Transperineal biopsy provides better cancer detection and detects more clinically significant cancers with less infection risk. However, transperineal biopsy also detects more insignificant cancers, is more painful, has more noninfectious side effects, and is an added cost to both practices and patients. There has been continued debate regarding the classification of Gleason 6 prostate cancer. Some of the arguments in favor of renaming it include that Gleason Grade Group 1 (GG1) is a common feature of aging, and as of 2023 it is nearly universally representative of overdiagnosis. It is effectively an incidental adverse effect of screening that is intended to find clinically significant cancers. In practice, GG1 that is found through MRI and liquid biomarkers is accepted as a nondiagnosis. GG1 is never a lethal diagnosis; it may precede diagnosis of a clinically significant cancer, but so can a negative biopsy. In opposition to renaming Gleason 6 are arguments that the community should acknowledge the issue of overtreatment. Through risk assessment, integration of traditional parameters, and future biomarkers, there might be no need to rename Gleason 6 prostate cancer, but the debate continues.

Presentations on genetic testing, new imaging technology, and clinical trials continue to move our field forward. The PROCLAIM trial, an observational patient registry, aims to assess whether national guidelines sufficiently identify men who may benefit from testing in primarily community urology practices.³ Fifty percent of the patients met the 2019 National Comprehensive Cancer Network Prostate Cancer criteria for germline genetic testing and 50% did not. The study found that patients who had germline genetic testing received significantly more recommendations for treatment, follow-up, and counseling for family members of pathogenic germline variants–positive patients. Germline genetic testing influenced prostate cancer patient care, including those patients who did not meet the National Comprehensive Cancer Network testing criteria for germline genetic testing. From an imaging standpoint, prostate-specific membrane antigen positron emission tomography (PSMA PET) has had a major impact on treatment decision-making for patients with prostate cancer. PSMA PET can be considered an alternative to conventional imaging for initial staging and at biochemical recurrence. PSMA PET in newly diagnosed unfavorable-intermediate and high-risk disease patients was found to change management in roughly 1 in 4 patients. The threshold for PSA for the best PSMA PET performance in biochemical recurrence is ∼.2 ng/mL in postsurgery patients; PSA kinetics should be used in postradiation patients. The EMBARK trial, a phase 3 randomized study, evaluated the efficacy and safety of enzalutamide with leuprolide acetate against placebo and leuprolide acetate as well as enzalutamide monotherapy in patients with high-risk biochemically recurrent prostate cancer.⁴ Enzalutamide combination showed a statically significant and clinically meaningful improvement in metastasis-free survival. Enzalutamide monotherapy also showed statistically significant and clinically meaningful improvements in metastasis-free survival, time to PSA progression, and time to first new antineoplastic therapy. Enzalutamide with androgen deprivation therapy has the potential to become a new standard of care for patients with high-risk biochemical recurrence.

Although huge strides have been made in the treatment and management of prostate cancer, there still exist significant disparities in outcomes for minority patients. There needs to be calibration of risk stratification tools for diverse populations. Guidelines are informed by data from resourced academic medical centers, but only one-third of studies contained demographic data at all. In the veteran population, it was found that transgender women had a higher median PSA density and percent with Gleason 4 or 5 for those patients on estrogen; is there a delayed diagnosis for those patients on estrogen? Agent Orange exposure may be associated with specific somatic tumor alterations in US veterans with prostate cancer. A multivariable analysis found that alterations in the androgen receptor were more frequent in those with Agent Orange exposure.

In the future, there should be more done to examine the disparities in health outcomes for patients with prostate cancer, with actions taken to limit the disparities. It was found that shared decision-making increases the prevalence of PSA screening for all men. It was found to have an even greater increase in PSA screening for Hispanic and non-Hispanic Black men. Initiatives to improve shared decision-making are warranted to increase guideline adherence and screening.

Conflict of Interest Disclosure: The Authors have no conflicts of interest to disclose.

Funding Source: The University of California, San Francisco, Goldberg-Benioff Program in Translational Cancer Biology.